In the United States, each year more than 700,000 people suffer from peripheral nerve injuries (PNI) that can lead to a lifelong disability, such as paralysis. The most frequent causes include motor vehicle accidents, gunshot wounds, stabbings, and birth trauma.
Currently, there are two gold standard treatments for nerve repair, which are end-to-end suturing and application of autograft or allograft biological tissue. However, each strategy suffers from a number of limitations. For example, end-to-end suturing cannot be performed when the nerve gap is larger than 1 cm. The use of autograft results in potential donor site morbidity for the patient and can potentially exacerbate the condition. The use of allograft tissue has an associated risk of immunogenicity.
Recent advances in tissue engineering and biomaterials suggest that there may be other approaches to nerve repair and regeneration that may overcome the limitations associated with harvesting natural tissues. One such approach would be the use of biomaterials to produce natural or synthetic nerve guidance conduits (NGCs). These NGCs may overcome some of the limitations of nerve autograft and allograft methods. The NGCs act as an essential precursor for nerve repair, since they can reduce tension at the suture line, can protect the regenerating axons from the infiltrating scar tissue, and can exhibit a low immune response. Although FDA-approved tissue engineered nerve devices have been available in the market for several years, these implant devices do not possess the proper physical topography or chemical cues for nerve repair and regeneration. Also, most of them are currently limited to a critical nerve gap of approximately 4 cm. To design an optimal NGC for enhancing PNR still remains a challenge.
Current laboratorial NGCs developed using haptotactic strategies alone are not yet comparable to autograft. For example, multichannel NGCs may have an insufficient cross sectional area and or inhibit cell-cell interaction between each of the individual channels. This may lead to functional mismatches and an insufficient level of regeneration. Controlling the position of inner filament bundles within NGCs has yet to be achieved, despite the fact that the presence of microfilaments has been demonstrated to enhance axonal regeneration and provide contact guidance for the regenerating axons in rats. Alternatively, microfilaments can mislead cell migration which can result in uneven distribution of cells within the NGC. These failures in NGCs may be attributed to the inadequate design of intra-luminal guidance channels/filament, forming incomplete fibrin cables during the initial stages of regeneration. Without the formation of this aligned bridge of extracellular material (ECM), further mechanisms for nerve repair are limited. Therefore, it still remains a challenge to design an optimal NGC for enhancing PNR, when compared to the use of autografts.